Causes & Symptoms – overview

Pathophysiology:

• Clinical manifestations: Signs vs. symptoms

• Etiology of a disease: Root cause vs. immune
response vs. homeostatic regulations
• Cell injury: effect of hypoxic injury, types of cell
death (necrosis vs. apoptosis)
Causes & Symptoms - Pathophysiology

Pathophysiology studies the disturbances of normal

physiologic functions related to illness, injury, and
disease.
Blood pressure of
Bone fracture 90/70mm Hg
Causes & Symptoms - Pathophysiology

Pathophysiology studies the disturbances of normal

physiologic functions related to illness, injury, and
disease.

1. Cultural
Considerations
2. Age
3. Gender
4. Situational
Differences
5. Time variations
Causes & Symptoms - Pathophysiology

Pathophysiology studies the disturbances of normal

physiologic functions related to illness, injury, and
disease.

1. Etiology – Cause of a phenomena (idiopathic = not known)

2. Pathogenesis – development of disease
3. Clinical manifestation – signs and symptoms of disease
4. Treatment implications – general treatment plan
Causes & Symptoms – Clinical
manifestation

Clinical manifestation – signs and symptoms of

disease:

Sign: Noticeable by observer, and usually measurable

Symptom: What the patient feels

Causes & Symptoms – Clinical
manifestation
Causes & Symptoms – Clinical
manifestation

Clinical manifestation – signs and symptoms of

disease:
Often occur in stages:
• Early stage: latent period (changes in cell biological
processes – might not yet felt by patient)
• Acute phase: full intensity of signs and symptoms
• Subclinical stage: organ function normal although disease is
established
• Convalescence: recovery after a disease – might result in
sequela (subsequent pathological conditions)
Causes & Symptoms – Clinical
manifestation

Clinical manifestation – signs and symptoms of

disease:

Clinical course of a disease:

• acute vs. chronic: short course of hours/ days/weeks vs.
month/years
• alternations of exacerbations and remission: alternations
of sudden increase in disease severity and decline in signs
and symptoms
Causes & Symptoms – Etiology

Etiology (Cause) & Pathogenesis (Development)

• Initial stimulus (Cause)

changes cell structure
and functions affect
tissue  organ  whole
body function
(Development:
expressed in clinical
manifestation)
Causes & Symptoms – Etiology

Etiology (Cause) & Pathogenesis (Development)

1. Root cause (etiologic factor): initial stimulus; leading to
direct cell or tissue damage; idiopathic = cause is unknown)

2. Immune response: common occurrences due to the

immune system reacting to the cell or tissue damage

3. Homeostasis disturbances: direct cell damage from root

cause and immune responses result in additional signs and
symptoms (sympathetic nerve activation)
Causes & Symptoms – Example
1. Etiology – Root Cause
2. Pathogenesis – immune response & homeostatic
disturbances (SNS)
3. Clinical manifestation – signs and symptoms of disease
4. Treatment implications – general treatment plan

Liam was recently exposed to Streptococcus and developed a

pharyngeal infection. His clinic examination reveals an oral
temperature of 102.3° F, skin rash, dysphagia, and reddened
throat mucosa with multiple pustules. He complains of sore
throat, malaise, and joint stiffness. His BP reads 80/60mmHg
and his heart rate is 130bpm. A throat culture is positive for
Streptococcus.
Causes & Symptoms – Cell Injury

Cell Injury: When cells lose function because of

disturbances, cellular injury has occurred.

Injury may be reversible or irreversible. Likelihood of reversal

decreases if:

a) Stimulus is highly injurious

b) Stimulus is intense
c) Stimulus is continued long-term
d) Affected cells are highly specialized (e.g. neurons)
e) Affected cells are otherwise compromised (cells
with poor nutritional status)
Causes & Symptoms – Cell Injury

Cell Injury: When cells lose function because of

disturbances, cellular injury has occurred.

1. Hypoxic injury is caused by lack of ability to use oxygen:

- often occurs because supply of blood to tissue

is interrupted (ischemia)

- can also arise from chemical interference of

mitochondrial biochemistry (e.g. cyanide poisoning
of electron transport chain)
Causes & Symptoms – Cell Injury

Cell Injury: When cells lose function because of

disturbances, cellular injury has occurred.

1. Hypoxic injury  Insufficient ATP production is the

primary mechanism:

1. Na, K-ATPase 3. Anaerobic

pump can’t eject
sodium ions from the
cytosol
2. Ca+2 ions accumulate
respiration is
increased in an
attempt to make up
the ATP shortfall
1. Hypoxic injury  Insufficient ATP production is the
primary mechanism:

1. Na, K-ATPase
pump can’t eject
sodium ions from the
cytosol
 1. Hypoxic injury  Insufficient ATP production is the
primary mechanism:

2. Ca+2 ions accumulate

a) Calcium can act in signal transduction  inappropriate

signaling disrupts cell biochemistry

b) Increased Calcium ions in mitochondria can trigger cell death

1. Hypoxic injury  Insufficient ATP production is the
primary mechanism:

3. Anaerobic
respiration is
increased in an
attempt to make up
the ATP shortfall
Causes & Symptoms – Cell Injury

Cell Injury: When cells lose function because of

disturbances, cellular injury has occurred.

1. Hypoxic injury  Insufficient ATP production is the

primary mechanism:

3. Anaerobic
Lactic acid accumulates  lowering
respiration is
cellular pH  DNA clumps and
increased in an
Lysosomes release enzymes
attempt to make up
digesting the cell
the ATP shortfall
Causes & Symptoms – Cell Injury

Cell Injury: When cells lose function because of

disturbances, cellular injury has occurred.

1. Hypoxic injury  Insufficient ATP production is the

primary mechanism:
 Reperfusion Injury (major source of
cellular injury that occurs as
hypoxia is relieved):
- Calcium overload
- free radicals
- Inflammation
Causes & Symptoms – Cell Injury

Might be
reversible

Cell death

Irreversible
injury
Causes & Symptoms – Cell Injury

Cell Injury: When cells lose function because of

disturbances, cellular injury has occurred.

1. Hypoxic injury
2. Chemical injury What are the effects of
3. Infectious injury cell injury?
4. Nutritional injury
5. Traumatic injury - Loss of function
- Infiltration (accumulation of
cell material)
- Cell death (Necrosis or
Apoptosis)
Causes & Symptoms – Cell Injury

Infiltration: synonym cellular accumulation; common

effect of chronic sorts of cellular injury
 metabolites that are not being properly handled
build up within the cells
steatosis
 Causes & Symptoms – Cell Injury
Alcoholic hepatomegaly

• Accumulation of
denatured proteins
• Accumulation of
endogenous
Tay-Sachs disease
material due to
faulty enzymes in
lysosomes
• Accumulation of
material that is
Carbon accumulation indigestible
Causes & Symptoms – Cell Injury

Cell death:
a) Necrosis (cellular death)
b) Apoptosis (intentional, programmed cellular suicide)
Causes & Symptoms – Cell Injury

Cell death (summary):

Causes & Symptoms – Summary
Pathophysiology studies the disturbances of normal physiologic functions
related to illness, injury, and disease
1. Etiology – Root Cause (initial stimulus)
2. Pathogenesis – immune response towards injury & homeostatic
disturbances (SNS) to compensate for injury
3. Clinical manifestation – signs and symptoms of disease; stages of
clinical course (early, acute, subclinical, convalescence  sequela,
chronic vs. acute)
4. Treatment implications – general treatment plan

Cell Injury (hypoxia caused by ischemia):

5. Osmotic imbalance due to ion imbalance (Na/K pump)  swelling
6. Ca++ disturbance  cell signaling & cell death
7. pH disturbance  lactic acid accumulation (fermentation)
 Acute (during hypoxia) and reperfusion injury (Ca overload, free radicals,
inflammation) leads to loss of function, infiltration and cell death
Causes & Symptoms – Summary
Cell death:
Necrosis: cell swelling & rupture of cell membrane  inflammation (large
area affected
Apoptosis: individual cell undergoes programmed death, Chromatin
condensation, cell shrinkage, cellular fragmentation (apoptotic bodies),
residues digested by immune cells (no inflammation)
Causes & Symptoms – study guide

Study guide:
1. What are the 4 interrelated topics of Pathophysiology?
2. Distinguish between signs and symptoms.
3. Be able to differentiate between different phases of clinical
manifestations.
4. Be able to approach pathophysiological problems in a systematic way
by considering direct, immune, and homeostatically-related disease
processes.
5. What is a risk factor?
6. Name some stimuli that result in irreversible cell injury.
7. What cellular processes do cells undergo following hypoxic insult?
Understand the underlying mechanisms (insufficient ATP production and
reperfusion injury) and effects (Infiltration and cell death) of cell injury
(hypoxic injury).