D’YOUVILLE COLLEGE
BIOLOGY 307/607 - PATHOPHYSIOLOGY
Lecture 3 - THERMOREGULATION/FEVER/HEALING
Chapters 3 & 4
1.
Thermoregulation:
• normal body temperature
- temperature of body core, 37o C, mainly monitored orally, rectally, in
external auditory canal, or in axilla
• negative feedback system for temperature regulation (fig. 3 – 2 & ppt. 1)
- thermoreceptors (sensors) detect change (up or down)
- sensory signal (input) delivered to hypothalamus
- input compared to ‘set point’ by hypothalamus; appropriate response
generated; signals sent to cerebral cortex (for behavioral response), to pituitary
(mediates thyroid response), and to various effectors (sweat glands, skin arterioles
(fig. 3 -- 1), skeletal muscles)
- responses alleviate deviation from ‘set point’ (reverse direction of change
= negative feedback) (fig. 3 – 3 & ppts. 2 & 3)
2.
Hyperthermia & Hypothermia:
• hyperthermia
- rise in core temperature (to 40.5o C or 105o F) may result from:
- environmental heat (warm, humid environment with poor ventilation)
outpaces normal regulatory mechanisms
- excessive heat production (overexertion at exercise)
- hypothalamic dysfunction
- may produce positive feedback (rise in metabolic rate produces more heat)
--> further rise in core temperature
• heat stroke:
- hot, dry skin due to dehydration & compromised sweating (anhydrosis);
(associated with hot climate = classic heat stroke)
- hot, clammy skin; (associated with excessive exercise = exertional heat
stroke)
Bio 307/607 lec 3
- p. 2 -
- multiple organ failure (brain, heart, kidney)
- treatment: apply cooling strategies (spraying, immersion) & rehydrate
Bio 307/607 lec 3
- p. 3 -
• hypothermia
- drop in core temperature (less than 35o C = mild hypothermia; less than 32o
C = severe hypothermia) from prolonged exposure to extreme cold
- low core temperature may produce positive feedback – depressed metabolic
rate (compromises heat production), depressed respiratory & heart rate, impaired
regulatory mechanisms  exacerbated decline in core temperature
- decline in metabolic demands (brain & heart) may outpace decline in
oxygen supply; results in prolonged survival despite moribund appearance
- euphoria or altered consciousness may produce bizarre behavior
- treatment: active application of warming strategies, especially inhalation
of warm moist air to raise neck (brain blood flow) and thoracic core temperatures
3.
Fever:
• pyresis (fever) – not failure of thermoregulation; instead, hypothalamic ‘set
point’ is elevated by the action of pyrogens
• endogenous pyrogens (EPs)– substances released (largely by macrophages) at
inflammation sites or within hypothalamus; may include interleukins, tumor necrosis
factor & interferons
- EPs may attach to nerve cells of vagus nerve that signal hypothalamus, or
may travel in bloodstream to hypothalamus
- EPs trigger elevation of set point through pathway involving
prostaglandins and other mediators (figs. 3 – 4, 3 – 5 & ppts. 4 & 5)
- thermoregulatory mechanisms then proceed as normal responding to new
set point
- fever stimulates immune function and phagocyte activity & diminishes
microbial reproductive capability
- prolonged fever may be dangerous to heart or stroke patients because
increased cardiac workload or increased rate of brain damage
- antipyretics (e.g. ASA, acetaminophen) alleviate fever by returning set
point to normal via inhibition of PG synthesis (fig. 3 – 6 & ppt. 6); cooling strategies
provide relief & help alleviate fever, especially cold cloths applied to nose and
forehead (by cooling blood flow to brain)
Bio 307/607 lec 3
4.
- p. 4 -
Healing:
• four processes: regeneration, repair, revascularization, and surface
restoration
• tissue components: functional cells (parenchyma) supported by connective
tissue & blood vessels (stroma)
• regeneration occurs via proliferation (mitosis) of normal surrounding cells,
which replace lost tissue and assume normal function; regenerative capability is
possessed by labile and stable tissues, but not by permanent tissues (fig. 4 – 1, table 4 -- 1
& ppt. 7)
- labile tissues normally maintain high mitotic activity (marrow, lymphoid
tissue, epidermis, mucous membranes) and regenerate rapidly
- stable tissues maintain slower mitotic activity (glandular tissue, smooth
muscle, bone, vascular endothelium), but may be stimulated to accelerate mitotic
activity
- permanent tissues have ceased (& cannot resume) mitotic activity, thus
are incapable of regeneration
• repair (scar formation or fibrosis) occurs in tissues that are unable to
regenerate (resulting tissue is nonfunctional)
- fibroblasts (connective tissue cells of stroma) produce new collagen and
extracellular matrix (ECM); ECM directs orientation and maturation of new
collagenous fibers -- maximizes tensile strength of the scar (fig. 4 – 3 & ppts. 8 & 9)
- organization involves phagocytic removal of clots and debris from injury
site, followed by replacement with scar; granulation tissue (fig. 4 – 5 & ppt. 10) is
associated with the granular appearance of protein-rich exudate in which new blood
vessels are developing (part of organization process mentioned above)
• revascularization involves endothelial budding of remaining healthy blood
vessels and coalescence of buds to establish new vascular network; additional wall
layers (of arterioles & venules) are added to outer surface(figs. 4 – 6, 4 – 7 & ppts 11 &
12)
• surface restoration: migration of epithelial cells from healthy edges of
wound to cover denuded injury site; granulation tissue often provides the
substratum for this process (fig. 4 - 8 & ppt. 13)
Bio 307/607 lec 3
- p. 5 -
• healing patterns: primary & secondary; patterns in various tissues
- primary healing occurs with small, narrow wounds, e.g., incisions; clot,
surface restoration, revascularization, scar formation, scab shed (fig. 4 - 9 & ppt. 14)
- secondary healing occurs with larger wounds and takes longer as more
granulation tissue is required (fig. 4 - 11 & ppt. 15); wound contraction distinguishes
this pattern: specialized myofibroblasts draw in edges of wound in predictable ways
(fig. 4 - 12 & ppt. 16); shape of wounds influences the shape of the resulting scar (fig.
4 – 13 & ppt. 17)
• summary of processes of healing: (ppt. 18)
• tissue variations:
- bone forms osteoid tissue (soft callus) composed of fibrocartilage from
osteoblasts; ossifies to hard callus that is remodeled by osteoclasts (fig. 4 - 14 & ppt.
19)
- glandular tissues (stable tissues), e.g., liver or kidney, may experience
some functional loss if extensive regeneration is required; with damage involving
parenchyma & stroma, surface depressions occur as repair produces scar (less
volume) where regenerative capacity is impaired
- nerve tissue: in central nervous system, glial cells produce non-functional
scar tissue; in peripheral nerves, regrowth is possible if neuron soma is undamaged
& supporting stroma can regenerate to form guide for regrowth of axons (fig. 4 - 16 &
ppt. 20)
- muscle tissue: scar replaces lost muscle cells; remaining live cells undergo
hypertrophy & damaged muscle cells may undertake regeneration of lost cell part if
stroma is intact
• complications of healing:
- contracture (fig. 4 - 17 & ppt. 21): due to exaggerated wound contraction
- adhesions: due fibrosis uniting adjoining serous membranes
- dehiscence: (usually abdominal): excessive pressure may reopen wound
before healing is complete; risk of infection, herniation
- keloids: due to excessive fibrosis producing raised welt on surface
- proud flesh: due to excessive development of granulation tissue; may
delay healing
• regulation of healing: growth factors, present in ECM promote growth &
differentiation of tissues involved in healing; ECM provides orientation at wound
Bio 307/607 lec 3
- p. 6 -
site as well as support for new healthy tissue growth; without ECM integrity no
regeneration is possible (fig. 4 - 20 & ppt. 22)