LICEO DE CAGAYAN UNIVERSITY WEEK: 3

COLLEGE OF MEDICAL LABORATORY SCIENCE DATE: SEPT 6, 2022

SUBJECT: General Pathology Lecture
TOPIC: Hemodynamic Disorders
TRANSCRIBED AND EDITED BY: KORICS RMT
FATA VIAM INVENIENT

HEMODYNAMIC DISORDERS: EDEMA, HYPEREMIA, AND CONGESTION

OVERVIEW WATER
 60% OF OUR BODY WEIGHT IS WATER
TERMS DEFINITION  2/3 OF WHICH IS INTRACELLULAR AND 1/3
EDEMA increased fluid in the ECF EXTRACELLULAR INTERSTITIAL
Hyperemia INCREASED flow  EXTRACELLULAR SPACE < INTRAVASCULAR
Congestion INCREASED backflow  BULK OF EXTRACELLULAR WATER IS FORMED BY
INTERSTITIAL FLUID AND ONLY 5% OF THE BODY’S
Hemorrhage extravasation WATER IS PRESENT AS BLOOD PLASMA
Hemostasis keeping blood as a fluid  Edema is
 If the net influx of fluid exceeds the lymphatic drainage, the excessive volume of
Thrombosis clotting blood fluid may accumulate either within the interstitial matrix (interstitial edema) or
Embolism downstream travel of a clot in the serous body cavities (effusion)
Infarction death of tissues w/o blood Edema – shift to the interstitial space
Shock circulatory failure/collapse terminology Body cavity involved
Hydrothorax Pleural cavity
EDEMA
Hydropericardium Pericardial cavity
- INCREASE IN EXTRACELLULAR FLUID
Hydroperitoneum (ascites) Peritoneal cavity
- An abnormal accumulation of fluid in the interstitial  Effusions, ascites, anascara
space within tissues
The edema fluid may be either transudate or exudate.
Pathophysiologic Categories of Edema
1. Transudate: It is protein-poor fluid caused by
MECHANISM CAUSES increased hydrostatic pressure or reduced
plasma protein.
Increased hydrostatic Impaired venous return Causes: Transudate is observed in heart
pressure (tends to drive - Generalized failure, renal failure, hepatic failure, and
water and salts out of the (Congestive heart failure, certain forms of malnutrition.

vessels into the interstitial Constrictive pericarditis)
space)
Decreased plasma osmotic
pressure (hypoproteinemia)
(which tends to drive water
and salts into the vessels)
Lymphatic obstruction (which
tends to drain the
interstitial space)
Sodium retention (sodium
retention increases
hydrostatic pressure and
causes a dilutional decrease
in the colloid osmotic
pressure
Inflammation
2. Exudate: It is protein-rich fluid produced due
- Regional to increased vascular permeability and is seen
in inflammation.
(Ascites in liver cirrhosis,
Obstruction (e.g. thrombosis) Differences between exudate and transudate
or compression of veins (e.g. Features Exudate Transudate
external mass), Arteriolar Definition Edema associated with Increase in vascular
increased vascular permeability observed
dilation: Heat) Filtrate of blood or
Nephrotic syndrome, Ascites plasma; no permeability
in cirrhosis of liver, Nature Inflammatory edema Non-inflammatory
Malnutrition, Protein-losing edema
gastroenteropathy Protein content 1. High (more than 4
g/dl 1. Low (less than 3
Inflammatory, Neoplastic, 2. 2. Has high g/dl)
Postirradiation, Postsurgical fibrinogen and 2. Mainly albumin, low
tendency to fibrinogen
coagulate
Excessive salt intake with
Specific gravity High (more than 1.018) Low (less than 1.015)
renal insufficiency, pH >7.3 <7.3
Increased tubular, ldh High Low
reabsorption of sodium: e.g. Fluid LDH/serum LDH Fluid LDH/serum LDH
ratio is >0.6 ratio is <0.6
increased renin-
Cells Highly cellular; rich in Few, mainly mesothelial
angiotensin-aldosterone polymorphs cells
secretion
Acute and chronic example Pus seen in pyogenic Fluid in congestive
infections cardiac failure
inflammation, angiogenesis

LOCALIZED AND GENERALIZED EDEMA
LOCALIZED EDEMA GENERALIZED EDEMA
- Limited to an organ or part
o Obstruction of vein or lymphatic:
For example edema of limb (usually
the leg) develops due to venous or
lymphatic obstruction caused by
thrombophlebitis, chronic
lymphangitis, resection of regional
lymph nodes, "lariasis, etc.
o Inflammation: It is the most
common cause of local edema.
o Immune reaction: For example
urticaria (hives), or edema of the
epiglottis or larynx (angioneurotic
edema).
Pneumonia (Inflammatory edema)
Chronic heart failure edema (chf)
Pulmonary edema
Two types of pulmonary edema:
1. Cardiogenic pulmonary edema
(caused by congestive
cardiac failure or left
ventricular failure which
lead to inadequate removal
of blood from the
pulmonary circulation)
2. Noncardiogenic pulmonary
edema (caused by injury to
lung parenchyma or
vasculature of the lung)
Renal edema
- Sodium retention
- Protein losing
glomerulonephritis
(nephrotic syndrome)
Subcutaneous edema It may be diffuse or more easily
- Anascara noticed in regions with high
- Left vs. right heart hydrostatic pressures. In most
- It is systemic in distribution and - Periorbital cases, the distribution of edema is
affects visceral organs and the - Pulmonary dependent on gravity and is
skin of the trunk and lower - Cerebral 9closed cavity, no termed dependent edema. Thus, it
extremities. expansion) is prominent in the legs when
- Causes: Disorder of fluid and o Herniation of standing, and in the sacrum when
electrolyte metabolism.
cerebellar tonsils recumbent. If pressure is applied
o Heart failure
o Nephrotic syndrome (renal o Herniation of by a finger over substantially
diseases with massive loss hippocampal uncus edematous subcutaneous tissue, it
of serum proteins into the over tentorium displaces the interstitial fluid and
urine) o Herniation leaves a depression. This sign is
o Cirrhosis of the liver. subfalcine called as pitting edema.
Hepatic ascites - PORTAL HYPERTENSION
- HYPOALBUMINEMIA
Differentiate between cardiac and renal edema:
Features Cardiac edema Renal edema
causes CHF and right-sided Nephritic and
heart failure nephrotic
syndrome/acute
tubular
injury/necrosis
mechanism Decreased cardiac Hypoalbuminemia and
- Increased venous pressure due to output decreased plasma
failure oncotic pressure
- Decreased renal perfusion, clinical Dependent edema, the First observed
triggering of renin-angiotensin- distribution of which around face, eyes,
aldosterone complex, resulting changes with posture ankle and genetalia
ultimately in sodium retention
Mainly pedal or
- Gross: The weight of lungs is sacral; later
increased 2 to 3 times of normal generalized
weight. Cut section shows frothy, Serum albumin normal decreased
blood-tinged fluid (due to mixture proteinuria absent present
of air, edema, and extravasated
red cells) oozing from the lung.
Microscopy: The edema fluid is seen
in the alveolar septa around
capillaries and reduces the
diffusion of oxygen. Edema fluid
present in the alveolar spaces
favors bacterial infection
- It can affect all parts of the
body. Initially, it is observed in
tissues with loose connective
tissue matrix, such as the eyelids
and scrotal region. Edema in the
eyelids is called periorbital edema
and is a characteristic of severe
renal disease.
- Causes: nephrotic syndrome,
glomerulonephritis, and acute
tubular injury.
Hyperemia and congestion - Hyperemia and congestion are characterized by Pulmonary congestion - defined as accumulation of fluid within the pulmonary
locally increased blood volume. interstitium as well as alveoli. It may be classified into ‘acute or chronic’ types
Hyperemia - An active process in which arteriolar based on duration.
dilation leads to increased blood flow to Acute Pulmonary Congestion - This may Gross Microscope
a tissue/organ. be cardiogenic or noncardiogenic in morphology features
origin. Lungs are The main
- Causes:
enlarged; cut histopathological
 Physiological: Response to increased
section shows features of acute
functional demand (e.g. heart and frothy, blood- pulmonary
skeletal muscle during exercise). stained fluid (air congestion are:
 Pathological: Seen in inflammation and is in combination  Alveolar septal
responsible for the two cardinal signs of with edema fluid edema
inflammation namely heat (calor) and and red cells).  Engorged
redness (rubor/erythema). septal
Congestion - A passive process resulting from reduced capillaries
venous outflow of blood from a  Focal intra-
tissue/organ. alveolar
- Types and Causes haemorrhages
1. Systemic: For example, congestive heart Chronic venous congestion (CVC) lung - Gross Microscope
failure, congestion involves liver, spleen, Long-standing pulmonary venous morphology features
congestion occurs due to left-sided - The lungs are - Dilatation and
and kidneys.
heart failure (eg, rheumatic mitral heavier and congestion of
2. Local: For example: stenosis), which results in increased
 Congestion of leg veins due to deep firmer than septal
pulmonary venous pressure. normal. capillaries
venous thrombosis
- Cut surface is - Intra-alveolar
 Edema of the lower extremity. dark brown in hemorrhage
 Local congestion at various sites due to color (brown (occurs due to
compression of veins, e.g. tight bandage, induration) rupture of
plasters, tumors, pregnancy, hernia, etc with oozing of congested
- Onset frothy, blood- capillaries)
 Acute: It develops during shock, or tinged - RBC breakdown
sudden right-sided heart failure. It may material. produces
occur in lung and liver. hemosiderin
 Chronic: It usually produces edema in the which is taken up
organ/tissue in which the venous outflow by alveolar
is reduced. macrophages.
 Appearance: Congested tissues have a These
hemosiderin-
dusky reddish-blue color (cyanosis)
laden
due to stasis of RBCs and the macrophages
accumulation of deoxygenated present in
hemoglobin. alveolar lumina
are called heart
failure cells
Differences between hyperemia and congestion (siderophages).
- Thickening and
Features Hyperemia Congestion fibrosis of
alveolar septae
Characterized by is eventually
Characterized by
blood pooling due to seen.
increased blood flow
Definition impaired
due to arteriolar Congestive splenomegaly - Long-term Gross Microscope
outflow/drainage from
dilation venous outflow obstruction leads to morphology features
tissue
congestive splenomegaly (splenic - Enlarged, - Congestion of
Nature of process active passive enlargement and congestion). Its causes tense and red pulp and
include portal hypertension (may be due cyanotic sinusoids
Appearance red Bluish-red/cyanosed to thrombosis of hepatic veins; also spleen with ultimately
Deoxygenated; tissue called to Budd-Chiari syndrome), thickening and causing
Type of blood Oxygenated cirrhosis, congestive heart failure or fibrosis of hemorrhage
hypoxia present
stenosis/thrombosis of the portal or capsule - Organization of
Edema Absent present splenic veins. hemorrhage
Local: portal venous results in
formation of
Menopausal flush, obstruction in cirrhosis
siderotic
examples muscular exercise, of liver; systemic: nodules (Gamna-
high-grade fever, etc. right-sided heart Gandy bodies)
failure
Hepatic congestion - Congestive hepatopathy refers to hepatic Evolution of hemorrhage
manifestations attributable to right-sided heart failure, Budd-Chiari
syndrome, hepatic sinusoidal obstruction syndrome, hepatic infarction and  Acute → chronic
ischemic hepatitis. Passive congestion often coexists with reduced cardiac
output.  Purple → green → brown
Acute hepatic congestion
Characterized by:  Hemoglobin → bilirubin → hemosiderin
- Dilated, distended central vein
and sinusoids Subdural hematoma - Subdural hematoma Causes: It is usually due to tear
- Central hepatocyte degeneration is defined as accumulation of blood in in the veins at the point where
- Fatty change in periportal the subdural space, i.e. between the inner they penetrate the dura matter.
hepatocytes (periportal surface of the dura mater and the outer be causes may be:
hepatocytes experience less arachnoid layer of the leptomeninges.  Fall
hypoxia - Venous bleeding between dura  road traffic accidents
- and arachnoid matter.  assaults
- because of proximity to hepatic - Commonly occurs due to rupture  Sport accidents.
arterioles, and therefore develop of bridging veins.
fatty change only)

Chronic passive congestion - the

central region of hepatocytic
lobules appears grossly red–brown
and slightly depressed with
surrounding zones of uncongested
liver (nutmeg appearance). Central
portion of hepatocytes being least
perfused, undergoes centrilobular
necrosis with loss or drop out of
hepatocytes. Severe long-standing
congestion may lead to grossly
evident hepatic fibrosis (cardiac
cirrhosis).
Hemorrhage - Extravasation of red cells due to vessel rupture is
called hemorrhage
Hemorrhage - hemothorax, - May be external (external
hemopericardium,
hemoperitoneum and
hemarthrosis (joints) - Haematoma may be nsignificant
- Acute or chronic
Hematoma vs. clot
Differences between antemortem (pre-mortem) and post-mortem clot
Features Antemortem / Post-mortem
premortem
Origin Formed as part of Form in a dead person
normal hemostasis or due to sedimentation
pathological and settling down of
derangement of blood components
clotting pathway in a
living person
gross  Dry, granular, firm  Gelatinous, soft
and friable and rubbery
 Lines of Zahn are  Dark red,
hemorrhage) or enclosed within
the tissue (when it is called a prominent in dependent portion
arterial thrombi of the clot is
hematoma).
called currant
(bruise) or large enough to cause jelly and yellow
fatality, eg, a large supernatant, free
retroperitoneal haematoma or an of red cells is
internal (visceral) haematoma called chicken fat
shape Do not form a cast of Take the shape of the
- Minute 1–2 mm hemorrhages into
the vessel vessel or its
the skin, mucous membranes or
bifurcation forms a
serosal surfaces are denoted as
cast of the vessel
petechiae (typically seen with
Attachment to vessel Present; strong Very weak
locally increased intravascular
wall
pressure, low platelet counts and
defective platelet function). location Anywhere in the body In dependent parts of
the body
- Larger >3 mm haemorrhages are
called purpura (associated Hemostasis
with the same disorders as Opposite of thrombosis - Preserve liquidity of blood
petechiae and also occur - “plug” sites of vascular injury
secondary to trauma, Three components 1) Vascular wall
2) Platelets
vasculitis or increased 3) Coagulation cascade
vascular fragility)
- Still larger >1–2 cm
subcutaneous haematomas or
bruises are called ecchymoses
(Generally seen after trauma).
 Sequence of events following vascular injury
1) Arteriolar vasoconstriction
2) Thrombogenic ecm
3) Tissue factor – released by
endothelium, platelets
4) Fibrin polymerizes, tpa limits
plug
Players – endothelium, platelets, and coagulation cascade
Endothelium - contain Weibel Palade bodies
- Endothelial cells play an important role in both homeostasis and
thrombus formation. they have both anti-thrombotic and
prothrombotic (procoagulant) properties. the balance between these
two opposing endothelial properties determines the thrombus
formation.
Normally / antithrombic properties
In injury Pro-coagulant properties
- Reflex neurogenic - Endothelial cells synthesize
- Endothelin, from endothelial cells tissue factor in response to
- Adhere and activate platelets cytokines [e.g. tumor necrosis
- Platelets aggregation (1˚ factor (TNF) or interleukin-1 (IL-1)]
or bacterial endotoxin. Tissue
hemostasis) factor activates the extrinsic
- Activates coagulation cascade → coagulation cascade.
- Activated endothelial cells
thrombin →fibrin (2˚hemostasis)
increases the catalytic function of
activated coagulation factors IXa
and Xa.
Prothrombic properties - Makes vwf (von williebrand factor),
which binds platelets→collagen
- Makes tissue factor (with
platelets)
- Makes plasminogen inhibitors
Antiplatelet properties - Activated by:
- they prevent platelet adhesion 1) Infectious agents
and aggregation following 2) Hemodynamics
 mechanism: 3) plasma
 Intact endothelium platelets
prevents adhesion of Alpha granules 1) Fibrinogen
platelets (and plasma 2) Fibronectin
coagulation factors) to the 3) Factor v, factor viii
highly thrombogenic 4) Platelet factor 4, tgf-beta
subendothelial ECM. Dense granules (dense bodies) 1) Adp/atp
 Production of inhibitors of 2) Ca+
platelet aggregation by 3) Histamine
endothelial cells: these 4) Serotonin
include: prostacyclin (PGI2), 5) Epinephrine
nitric oxide (NO) and * with endothelium, form tissue factor
adenosine diphosphatase Platelets phases
(which degrades adenosine
diphosphate-ADP).
1) Adhesion
Anticoagulant properties 2) Secretion (i.e.,
- The endothelium inhibits “release” or
coagulation by following ”activation” or
molecules: “degranulation”
 Heparin-like molecules: Found in 3) aggregation
the endothelium and exert their
anticoagulant effect indirectly Platelet phases
through antithrombin III. They Adhesion
inactivate thrombin and - PRIMARILY TO THE SUBENDOTHELIAL ECM
coagulation factors (Xa and IXa). - REGULATED BY VWF, WHICH BRIDGES
PLATELET SURFACE RECEPTORS TO ECM
 thrombomodulin: Present on the COLLAGEN
endothelial cells and binds to Secretion – (i.e. “release”oR ”activation” or
thrombin and activates protein C, “degranulation”)
which inhibits clotting by - BOTH GRANULES, ALPHA AND GAMMA
proteolysis of factor Va and - BINDING OF AGONISTS TO PLATELET
VIIIa. SURFACE RECEPTORS AND INTRACELLULAR
PROTEIN PHOSPHORYLATION
 Tissue factor pathway inhibitor
Aggregation
(TFPI): Inhibits tissue - ADP
factor/factor VIIa complexes. - THROMBOXANE A2
- THROMBIN FROM COAGULATION CASCADE
- FIBRIN FURTHER STRENGTHENS AND
HARDENS AND CONTRACTS THE PLATELET
PLUG
Fibrinolytic properties
- Endothelial cells synthesize
tissue-type plasminogen activator
(t-PA) which degrades whenever a
thrombi is formed.
 Platelet events
1) Adherence to ecm Coagulation cascade
- intrinsic (contact0 / extrinsic
2) Secretion of adp and (tissue factor)
txa2 - proenzymes → enzymes
3) Expose phospholipid
- prothrombin (ii) → thrombin (iia)
cpmplexes
4) Express tissue factor - fibrinogen (i) → fibrin (ia)
- cofactors
5) Primary → secondary  ca++
plug  phospholipid (from platelet
6) Strengthened by fibrin membranes)
 vit. K dep. Factors: ii, vii, ix, x,
Coagulation cascade protein s, c, z
Intrinsic pathway
- assessed in
vitro by the coagulation tests
thrombus – solid mass
activated - (a)ptt → intrinsic
formed → composed of:
partial - Pt (inr) → extrinsic
aggregate of
thromboplasti - Bleeding time coagulated blood
n time (aPTT) (platelets) → 2-9 mins containing platelets,
- Platelet count fibrin, and entrapped
(normal value: 150,000 – cellular elements of
400,000/mm3) blood
- Fibrinogen
- Factor assays

Thrombosis - the process of formation of a solid mass in the circulating

blood from the constituents of flowing blood.
* pathogenisis, endothelial injury, alterarions in flow, hypercoagulability, morphology, fate, clinical
correlations, venous, arterial (mural)
Virchow’s triangle (PG 116; NAYAK’S)
Extrinsic pathway
- assessed by
the
prothrombin
time (PT)

Common pathway
1) injury to endothelium → changes in
the vessel wall
2) Stasis or turbulent blood flow /
abnormal flow (non laminar) →
changes in the blood flow
3) Hypercoagulability → changes in the
blood itself
Virchow’s triad / triangle
1) Endothelial injury (PG 116) - Any pertubation in the dynamic
 Physical damage balance of the pro- and
 Endothelial dysfunction (or antithrombic effects of
activation) endothelium, not only physical
“damage”
2) ABNORMAL FLOW / STASIS (PG 117) - NONLAMINAR FLOW 2) EMBOLIZATION - propagating tail fragments
- TURBULENCE give rise to emboli
- EDDIES
- STASIS
3) DISSOLUTION - fibrinolysis usually on the
- “DISRUPTED” ENDOTHELIUM first or second day
ALL OF THESE FACTORS MAY BRING 4) ORGANIZATION - ingrowth of endothelial
PLATELETS INTO CONTACT WITH cells, smooth muscle and
ENDOTHELIUM AND/OR ECM fibroblasts
3) 1˚HYPERCOAGULABILITY (INHERITED) - MOST COMMON: FACTOR V AND
5) RECANALIZATION - New lumen/channels lined by
PROTHROMBIN DEFECTS
- COMMON: MUTATION IN PROTHROMBIN endothelial cells may form
GENE, MUTATION IN in an organized thrombus.
METHYLTETRAHYROFOLATE GENE #ese capillary channels may
- RARE: ANTITHROMBIN III DEFICIENCY , form thoroughfare channels
PROTEIN C DEFICIENCY, PROTEIN S and can re-establish the
DEFICIENCY
continuity of the original
- VERY RARE: FIBRINOLYSIS DEFECTS
- PROLONGED BED REST OR
lumen.
4) 2˚HYPERCOAGULABILITY (ACQUIRED)
IMMOBILIZATION  INFLAMMATION AND FIBROSIS →(central liquefaction, bacterial seeding and influx of
- MYOCARDIAL INFARCTION inflammatory cells)
- ATRIAL FIBRILLATION  Lines of zahn → alternating light (pale or white) area of platelets held together by
- TISSUE DAMGE (SURGERY, FRACTURE,
BURNS) FIbrin, and dark retracted area of FIbrin meshwork with trapped RBCs. They help to
- CANCER (TROUSSEAU SYNDORME, distinguish antemortem thrombus from postmortem clot.
MIGRATORY THROMBOPHLRBITIS)
- PROSTHETIC CARDIAC VALVES Dvt (deep vein Arterial/cardiac Dic (disseminated
- DISSEMINATED INTRAVASCULAR thrombosis) thrombi intravascular
COAGULATION coagulation)
- HEPARIN-INDUCED THROMBOCYTOPENIA - Deep (calf, thigh, pelvic) - Acute myocardial - Obstetric
- ANTIPHOSPHOLIPID ANTIBODY SYNDORME vein thrombosis infarction = old complications
(LUPUS ANTICOAGULANT SYNDROME)
 RISK FOR THROMBOSIS: - Chf, a huge factor atherosclerosis + - Advanced malignancy
 CARDIOMYOPATHY - Inactivity fresh thrombosis - Shock
 NEPHROTIC SYNDROME - Trauma - Arterial thrombi also o Not a primary disease
 PREGNANCY - Surgery may send fragments o Consumptive
 ORAL CONTRACEPTIVE USE - Burns downstream, but coagulopathy:
 SICKLE CELL ANEMIA - Injury to vessels these fragments may reduced platelets,
 SMOKING, OBESITY
MORPHOLOGY
- Procoagulant contain flecks of fibrinogen, factor viii,
Layers in thrombus: substances from tissues plaque also and other
– First layer of the thrombus on the endothelium/endocardium is a platelet layer. - Reduced t-pa activity - Lodging is consumable clotting
– On top of the platelet layer, FIbrin is precipitated to form upstanding laminae which proportional to the % factors, brain, heart,
anastomose to form an intricate structure which resembles coral (coralline thrombus). of cardiac output the lungs, kidneys,
In between the upstanding laminae and anastomosing Fibrin meshwork, the red blood organ receives, i.e., microscopic only
cells get trapped. Retraction of FIbrin produces a ribbed appearance on the surface of brain, kidneys, spleen,
thrombus.
legs, or the diameter
ADHERENCE TO VESSEL WALL - HEART (MURAL)
- ARTERY (OCCLUSIVE/INFARCT) of the downstream
- VEIN) vessel
OBSTRUCTIVE VS. NON-OBSTRUCTIVE

COLOR RED, YELLOW, GREY/WHITE

ACUTE, ORGANIZING, OLD
MURAL THROMBI - attached to one wall of an underlying
structure, usually capacious lumina of
heart chambers and aorta.

FATE OF THROMBI
1) PROPAGATION - accumulation of additional
platelets and fibrin leading
to progression

Different types of emboli
Physical nature of the emboli
Presence or absence of
secondary infection
Site of origin
embolism
- Solid: Thromboemboli,
atheromatous material, tumor
emboli, tissue fragments,
bacterial clumps or parasites,
foreign bodies.
- Liquid: Fat, bone marrow and
amniotic fluid.
- Gaseous: Air or other gases.
- Bland: Sterile.
- Septic: Infected.
- Cardiac emboli → left side of
heart
- Arterial emboli → atheromas
and aneurysms
- Venous emboli → deep vein
thrombosis
- Lymphatic emboli → tumour
Systemic emboli - “paradoxical” emboli
- 80% cardiac; 20% aortic
- Embolization lodging site is
proportional to the degree of
flow (cardiac output) that area or
organ gets, i.e., brain, kidneys, legs
Other emboli - Fat → long bone structure
- Air → scuba bends
- Amniotic fluid → very prolonged or
Infarction - An area of necrosis secondary to
decreased blood flow
- Hemorrhagic vs. anemic
- Red vs. white → end arteries vs. no
end arteries
- Acute → organization → fibrosis
Infarction factors - Nature of vascular supply
- Rate of development → slow
(better) / fast (worse)
- Vulnerability to hypoxia → myocyte
vs. fibroblast / Chf vs. no chf

emboli

Flow of emboli - Paradoxical emboli/crossed

emboli: Emboli crossing over
from venous circulation to
arterial circulation or vice-
versa; deep leg vein emboli
cross to pulmonary circulation
and then to systemic arterial
circulation.
- Retrograde emboli: Travel
against the direction of blood
flow, eg, retrograde spread of
prostatic carcinoma to spine
via intraspinal veins.
Increased pressure in the
body cavities during coughing
or straining carries emboli
from large thoracic ducts and
abdominal veins.
Embolism
- Pulmonary, Systemic (mural
thrombi and aneurysms), Fat, Air,
Amniotic fluid

Pulmonary embolism - Usually salient

- Chest pain, low po2, shortness of
breath
- Sudden occlusion of >60% of
pulmonary vasculature, presents a
high risk for sudden death
i.e., acute cor pulmonale, acute
right heart failure
- “saddle” embolism is often or
usually fatal
- Pre vs. post mortem blood clot:
o Pre: friable, adherent, lines of
zahn
Post: currant jelly or chicken fat
Shock
*pathogenesis (cardiac, septic, hypovolemic), morphology, clinical course
Shock
Common pathophysiologic features:
General results
Types of shock
Cardiogenic shock
- acute/chronic heart failure
- Most commonly due to acute
myocardial infarction
Hypovolemic shock
- Hemorrhage or leakage
Septic shock
- “endotoxic” shock
- #1 killer in icu
 Overwhelming infection
 Peripheral vasodilation
 Pooling
 Endothelial activation
 Dic
 think of this as a total body
inflammatory response
 endotoxins
 usually gram-negative
bacteria
 degraded bacterial cell wall
products
 also called “lps” because
they are lipo-poly-
saccharides
 attach to a cell surface
antigen known as cd-14
- A pathological process that
results from inadequate tissue
perfusion, leading to cellular
dysfunction and organ failure.
- Cardiovascular collapse
- Inadequate cardiac output
- Inadequate blood volume
- Inadequate tissue perfusion
- Cellular hypoxia
- Uncorrected → fatal outcome
- Intrinsic myocardial damage: For
example, massive myocardial
infarction, ventricular
arrhythmias.
- Extrinsic pressure or compression
of heart: For example, cardiac
tamponade.
- Obstruction to the out flow blood
from ventricles: For example,
pulmonary embolism.
- Loss of blood: For example, massive
hemorrhage.
- Loss of plasma: For example,
severe burns.
- Loss of fluid: Vomiting, diarrhea,
severe gastroenteritis, E.g.
cholera.
- Shock due to severe sepsis with
hypotension, which cannot be
corrected by infusing fluids.
- Septic shock results from
vasodilation and peripheral
pooling of blood and is associated
with dysfunction of multiple
organs distant from the site of
infection.
- Causative organisms:
- Gram-positive (most common) or
gram-negative bacteria, fungi, and
very rarely, protozoa or
rickettsiae
- common gram-positive bacteria
 Staphylococcus aureus
 Enterococci
 Streptococcus pneumoniae
- gram-negative bacilli → resistant
to usual antibiotics
 E. coli
 Proteus
 Klebsiella
 Pseudomonas
- superantigens →polyclonal T
lymphocyte activators that induce
release of high levels of cytokines
that lead to vasodilatation,
hypotension and shock
* more info on nayak’s pg 132
Neurogenic shock Occurs due to loss of vascular tone
- Loss of vascular and peripheral pooling of blood
following anesthesia or spinal cord
injury.
Anaphylactic shock Occurs when an allergic response
- IgE mediated systemic vasodilation triggers a quick release of mast cell
and increased vascular permeability mediators in large quantities
(histamine, prostaglandins and
leukotrienes) leading to systemic
vasodilatation (associated with
hypotension), increased vascular
permeability and
bronchoconstriction (leading to
difficulty in breathing). Shock can
lead to death in a matter of minutes
if left untreated.
Septic shock events (linear sequence)
Systemic vasodilation (hypotension) → decrease myocardial contractility →
diffuse endothelial activation → leukocyte adhesion → alveolar damage →
ards
- dic
- vital organ failure → cns
Clinical stages of shock
1) Non-progressive (initial, - During the initial phase,
compensated, and reversible) homeostatic compensatory
phase mechanisms redistribute the blood
- compensatory mechanism supply in such a way that the
- catecholamines effective blood supply to the vital
- Vital organs perfused organs is maintained. This is achieved
by neurohumoral mechanisms, which
try to maintain cardiac output and
blood pressure.
- Compensatory changes: The
neurohumoral mechanism
produces the following
compensatory changes:
- Widespread vasoconstriction
except vital organs.
Coronary and cerebral vessels
usually maintain relatively normal
blood flow, and oxygen delivery.
Cutaneous vasoconstriction →
produces the coolness and pallor
of the skin.
- Fluid conservation by kidney.
- Tachycardia.
2) Progressive - If the underlying causes are not
- hypoperfusion corrected, shock passes to the
- Early “vital” organ failure progressive phase.
- oliguria
- acidosis - Characterized by widespread tissue hypoperfusion
and hypoxia → intracellular aerobic respiration
replaced by anaerobic glycolysis → increased
production of lactic acid → metabolic lactic acidosis
→decreases the tissue pH → dilatation of
arterioles peripheral pooling of blood into the
microcirculation → decreases the cardiac output →
produces anoxic injury to endothelial cell →
favors development of DIC → widespread tissue
hypoxia and damage of vital organs.
3) irreversible - Without intervention, the shock
- hemodynamic corrections of no eventually enters an irreversible
use stage.
- At this phase, cellular and tissue
injury is so severe that even if the
hemodynamic defects are corrected,
survival is not possible.
- Widespread cell injury results in
leakage of lysosomal enzymes, which
aggravate the shock state.
- Myocardial contractile function
worsens partly due to nitric oxide
synthesis.
- If ischemic intestine allows
microbes from the intestinal flora
to enter into the circulation, it may
lead to superimposed bacteremic
shock.
- The patient develops acute tubular
necrosis and results in death.

Clinical progression of symptoms

- hypotension
- tachycardia
- tachypnea
- warm skin → cyanosis
- renal insufficiency
- obtundation
- death