THE HEART - Seven major categories of cardiac diseases in bold

 

I.              Congestive Heart Failure (CHF)

A.     The common end point of many different types of heart disease

B.     Multisystem derangement that occurs, in most cases, when the heart is no longer able to eject the blood delivered to it by the venous system

C.     Most common causes of left-sided cardiac failure

1.     Systemic HTN

2.     Mitral or aortic valve disease

3.     Ischemic heart disease

4.     Primary diseases of the myocardium

5.     (Leads to pulmonary edema)

D.     Most common cause of right-sided heart failure is left ventricular failure, other causes:

1.     Cor pulmonale

2.     Primary diseases of the pulmonary vasculature

3.     Pulmonic or tricuspid valve disease

4.     (Leads to nutmeg liver and anasarca)

E.     Compensatory mechanisms (compensated heart failure)

1.     Increased activity of sympathetic nervous system

2.     Hypertrophy

3.       End-diastolic pressure and volume increase®dilation of heart

4.     Elongation and stretching of individual cardiac muscle fibers (w/initial Frank-Starling response)

F.     Decompensated heart failure

1.     Progressive decrease in myocardial contractility

2.     Declined cardiac output

3.     Decreased perfusion kidneys®renin-angiotensin system

4.     Increased aldosterone output

5.     Positive feedback

II.         Ischemic Heart Disease - Coronary artery (heart) disease

A.     Most common cause atherosclerosis of coronary arteries

B.     Becomes symptomatic at 75% or greater occlusion

C.     In addition to fixed atherosclerotic plaques, myocardial ischemia affected by superimposed lesions:

1.       Acute changes in morphology of chronic atherosclerotic plagues

a)     Fissuring

b)     Hemorrhage into the plaque

c)     Rupture with embolization of atheromatous debris

d)      Increased risk of platelet aggregation and thrombosis

2.     Local platelet aggregation

a)     Mechanical occlusion

b)       Coronary vasospasm [from endothelial mediators]®occlusion

3.     Coronary artery thrombosis®infarct

4.       Coronary artery spasm, associates with Prinzmetal’s (variant) angina

D.     Four resultant syndromes

1.     Angina Pectoris - intermittent chest pain caused by reversible myocardial ischemia

a)     Typical (stable) angina pectoris (crushing feeling)

b)       Prinzmetal's (variant) angina (occurring at rest)

c)       Unstable (crescendo) angina pectoris

i.                With slightest exertion

ii.            a.k.a. preinfarction angina

2.     Myocardial Infarction - development of defined area of myocardial necrosis caused by local ischemia

a)     Typically begin in the subendocardial region

b)       Signs and symptoms

i.                Severe, crushing substernal chest pain

ii.            May radiate to neck, jaw, epigastrium, shoulder, left arm

iii.        Angina pectoris of several hour to days long

iv.            Dyspnea

v.                Cardiogenic shock

vi.            EKG abnormalities

c)     Complications of a transmural MI

i.              Papillary muscle dysfunction

ii.            Rupture of infarcted papillary muscle

iii.        External rupture of the infarct

iv.            Rupture of the intraventricular septum

v.                Mural thrombi

vi.            Acute pericarditis

vii.        Ventricular aneurysms

d)       Subendocardial MI restricted to the inner 1/3 of myocardium

e)       Necrosis **20-30 minutes

i.              Early coagulative begins by about 4-12 hours

ii.            Coagulative (pyknosis) necrosis in 12-18 hours

iii.        Complete coagulation necrosis in 24-72 hours

f)     Arteries most affected

i.                Left anterior descending coronary (40-50%)

ii.            Right coronary (30-40%)

iii.        Left circumflex coronary (15-20%)

g)     Lab findings in support of MI

i.              Creatine kinase® CK-MB most specific indicator of MI

ii.         Lactate dehydrogenase

iii.    Serum levels of certain myocardial proteins

3.       Chronic Ischemic Heart Disease with congestive heart failure

4.       Sudden Cardiac Death

III.    Hypertensive Heart Disease

IV.            Cor Pulmonale - Heart disease caused by intrinsic pulmonary diseases

 

 

 

 

 

V.              Valvular Heart Diseases

A.     Rheumatic Fever and Heart Disease

1.     Etiology group A streptococcal pharyngitis

2.     Hypersensitivity reaction against M proteins

3.     Two to three weeks allows antibody development

4.     Antibodies attack heart valves in multiple foci of inflammation, Aschoff bodies - containing a central focus of fibrinoid necrosis, surrounded by a chronic mononuclear inflammatory infiltrate, and occasional large histiocytes with vesicular nuclei and an abundant basophilic cytoplasm, Anitschkow cells

5.      Most commonly affects left heart valves, mitral and aortic

B.     Calcific Aortic Stenosis

1. Sclerosis and calcification of the aortic valve most common cause of isolated aortic stenosis in the U.S.
- a.k.a.  degenerative calcific aortic stenosis (DCAS)

2. Prophylactic antibiotic therapy is important because death occurs 3-4 years after the onset of symptoms

C.     Mitral Valve Prolapse

D.     Nonbacterial Thrombotic Endocarditis (NBTE)

1.     Characterized by the deposition of small masses of fibrin, platelets, and other blood components on the leaflets of the cardiac valves

2.     Lesions of NBTE are sterile and contain no microorganisms

3.      Marantic endocarditis - term for increased frequency of NBTE in cachectic (general debility or wasting) patients

4.     Lambl's excrescences - resolved lesions that leave delicate strands of fibrous tissue

E.     Infective Endocarditis

1.     Most common organisms

a)     Staphylococcus aureus

b)     a-hemolytic streptococci

c)     HACEK group (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella)

d)     Staphylococci epidermidis

e)     Gram negative bacilli and fungi

2.     Acute - infection of valves by highly virulent organisms such as Staphylococcus aureus

3.     Subacute - infection of previously abnormal valves by lower virulent organisms such as a-hemolytic streptococci

F.     Prosthetic Cardiac Valves

 

 

 

 

VI.         Primary Myocardial Diseases

A.     Myocarditis – inflammation

1.     Infections (viruses, chlamydia, rickettsia, bacteria, fungi, protozoa, helminths)

2.     Immune-mediated reactions

3.     Unknown (sarcoidosis, giant cell myocarditis)

B.     Cardiomyopathies - heart disease resulting from a primary abnormality in the myocardium

1.     Dilated cardiomyopathy

a)     Progressive cardiac hypertrophy, dilation [of all chambers] and contractile (systolic) dysfunction

b)     Result of:

i.              Viral nucleic acids

ii.         Alcohol abuse

iii.    Toxic insult (cobalt)

iv.         Peripartum cardiomyopathy, occurs late in pregnancy or post partum

v.              Idiopathic

2.     Hypertrophic cardiomyopathy

a)     a.k.a. asymmetric septal hypertrophy and idiopathic hypertrophic subaortic stenosis

b)     Most pronounced in the left ventricle and septum

c)       Most common in sudden unexplained death of young athletes

3.     Restrictive cardiomyopathy

a)      Primary decrease in ventricular compliance, resulting in impaired ventricular filling during diastole

b)     Most common cause - endomyocardial fibrosis Löffler’s syndrome - eosinophilic endomyocardial fibrosis

i.               Proteins released from degranulating eosinophils

ii.         Atria typically dilate

iii.    Endocardium thickened and opaque

c)     Also caused by cardiac amyloidosis, hemochromatosis and radiation injury

d)     Stiff and inelastic ventricle that can fill only with great effort

 

 

 

 

 

 

 

 

 

 

 

 

 

 

VII.    Congenital Heart Disease

A.     Left-to-Right Shunts - most common type of CHD Cyanosis is not an early feature, but it may occur late

1.     Atrial septal defects

2.     Ventricular septal defects - most common type of L®R

3.     Patent ductus arteriosus

B.     Right-to-Left Shunts **Cyanosis is an early feature: results from poorly oxygenated blood from the right side entering directly into the arterial circulation

1.      Tetralogy of Fallot - most common cause of cyanotic CHD

2.       Transposition of the great arteries - incompatible with life

C.     Congenital Obstructive Lesions

1.     Coarctation of the aorta

a)     Fairly common

b)     Two types

i.              Preductal (infantile) - congestive heart failure, selective cyanosis lower extremities, weak femoral pulse

ii.         Postductal - clinicals in older children and adults; hypertension of the upper extremities (resulting from low perfusion kidneys®renin-angiotensin activation), low BP in lower extremities, arterial insufficiency in legs (intermittent claudication)

VIII.                       Pericardial Diseases

A.     Pericarditis

1.     Acute P~ (a.k.a. shaggy heart, bread and butter pericarditis)

a)     Viruses most responsible, also SLE, rheumatic fever, and metastases

b)     Uremia most common systemic disorder

2.     Chronic P~

a)     Formation of delicate adhesions to dense, fibrotic scars that obliterate the pericardial space

b)     Can lead to constrictive pericarditis

B.     Pericardial Effusions

1.     Serous - CHF and hypoalbuminemia

2.     Serosanguineous - blunt chest trauma, malignancy

3.     Chylous - lymphatic obstruction

4.     Hemopericardium - rupture aortic aneurysm, myocardial infarcts, penetrating injury

5.     Leads to cardiac tamponade and death

IX.         Cardiac Tumors

A.     Metastatic Neoplasms

1.     Most common

2.     Most often involves the pericardium

3.     Most often come from the lung and breast, malignant melanomas, and hematopoietic malignancies

B.     Primary Neoplasms

1.     Rare

2.      Most common are myxomas, lipomas, cardiac rhabdomyomas

Blood vessels

 

I.              Note general properties of endothelial cells and vascular smooth muscle

II.         Arterial disorders

A.     Arteriosclerosis - thickening and inelasticity of arteries

1.     Atherosclerosis - most predominant form of arteriosclerosis

a)     First world nation predominant

b)     Constitutional risk factors - immutable (major non-modifiable)

i.              Age

ii.         Sex

iii.    Familial predisposition

c)     Acquired risk factors - major modifiable

i.              Hyperlipidemia

ii.         Hypertension - 140/90

iii.    Cigarette smoking

iv.         Diabetes

d)     Soft risk factors - minor modifiable

i.              Insufficient physical activity

ii.         Stressful life style (type a personality)

iii.    Obesity

iv.         Use of oral contraceptives

v.              Hyperuricemia

vi.         High carbohydrate intake

vii.    Hyperhomocysteinemia

e)     Plaque formation: endothelial dysfunction,
monocyte adhesion and infiltration, smooth muscle proliferation, extracellular matrix deposition, lipid accumulation, and thrombosis

f)     Morphologies

i.              Fatty dot - intimal discoloration

ii.         Fatty streak - elongated fatty dots

iii.    Atheroma - mainly intracellular lipid with a core of extracellular lipid

iv.         Fibrofatty atheroma - lipid core and fibrotic layer singly or layered or calcific

v.              Atheromatous plaque - hallmark of arteriosclerosis

2.     Mönckeberg’s medial calcific sclerosis

3.     Arteriolosclerosis - see b. Hypertension

 

 

 

 

B.     Hypertension and hypertensive vascular disease

1.     Potential mechanisms ® aberrations of normal regulatory processes.
Arterial HTN occurs when changes develop that alter the relationship between blood volume and total arterial resistance

2.     1°  º idiopathicº140/90º[essential] hypertension

a)     Genetic factors

b)     Environmental factors

3.     2° º result of another condition

4.     Benign º stable, modest HTN w/o MI or CVA

5.     Malignant º ?/120 BP; rapidly rising; death in 1-2 years; 1° or 2°

6.     BP = cardiac output x peripheral resistance

a)     CO results from volume; primarily by sodium control

b)     PR results from lumen size

i.              Vasodilators

ii.         Vasoconstrictors

c)        Renin (JGM ce11s) ® angiotensin I (plasma) ® angiotensin II (lung)

i.              Affects pr by causing vasoconstriction of VSC

ii.           Affects co by stimulating aldosterone secretion

7.     Vascular pathology in HTN

a)     Most predominant in the kidneys [and other organs]

b)     Hyaline arteriolosclerosis - homogeneous, pink, hyaline thickening of arteriole walls

i.              Frequent in elderly

ii.         Benign nephrosclerosis

c)     Hyperplastic arteriolosclerosis

i.              Associated more with malignant HTN

ii.         Onion-skin, concentric, laminated thickening of arteriole wall

iii.    Necrotizing arteriolitis - deposits of Fibrinoid and acute necrosis of vessel walls

C.     Vasculitis - inflammatory involvement of artery, vein, or venule

1.     Polyarteritis Nodosa (pan) - panmural acute necrotizing arteritis with fibrinoid necrosis, neutrophil and eosinophil infiltration, and extension into adventitia

a)     Medium to small arteries in any organ (except lung)

b)      Sharply segmental lesions of nodular aneurysmal dilation

c)     GI tract, liver, kidney, pancreas, muscles, other

d)      May coexist in different or within the same vessel(s)

2.        Wegener's granulomatosis - acute and chronic (sometimes granulomatous) angiitis with prominent eosinophils and occasional giant cells in association with extravascular granulomas

a)        Small to medium-sized arteries

b)        Upper and lower respiratory tracts; occasionally eye, skin, heart

c)     Necrotizing granuloma

 

3.     Microscopic polyangiitis - necrosis and neutrophilic infiltration of venules with leukocytoclasis -(fragmented neutrophils that follow vessel wall)

a)     Venules, capillaries, arterioles

b)     Widespread, but mostly skin

4.     Temporal (giant cell, cranial) arteritis - chronic mononuclear inflammatory infiltration, mostly in inner half of the media, with giant cells and granuloma formation

a)     Elastic tissue - rich major arteries of head

b)     Head, including ocular and intracranial vessels; uncommonly systemic

5.     Takayasu's arteritis (pulseless disease) - chronic vasculitis that affects principally the aorta and its main branches and sometimes the pulmonary arteries

a)     Mostly women; mostly upper extremity

b)     Once erroneously Asian origin - now known globally

c)     Thickening aortic wall resulting in lack of pulse

6.     Kawasaki's disease - acute and chronic infiltration mainly with lymphocytes and macrophages, and with endothelial cell necrosis and immunoglobulin deposition

a)     Acute febrile illness of infancy

b)     Small and medium-sized arteries

c)     Skin, ocular and oral mucosa, coronary arteries, may be widespread

7.     Thromboangiitis Obliterans (Buerger’s disease) -sharply segmental acute and chronic inflammatory infiltration of arteries and veins, often with giant cells, granulomas, intravascular thrombi containing microabscesses, and later perivascular fibrosis trapping nerve trunks

a)     medium-sized and small arteries and veins

b)      extremities - principally tibial and radial arteries

c)     male cigarette smokers age 25-50

d)     often preceeded by Raynaud’s phenomenon

 

 

 

 

 

 

 

 

 

 

 

D.     Aneurysms - dilation of arteries or veins that develop wherever there is marked weakening of the vessel wall

1.     Anatomical classifications

a)     Saccular - balloon-like

b)     Fusiform - general widening to general narrowing

c)     Cylindroid - sudden widening to sudden narrowing

d)     Berry-shaped - little ball

e)     saccular berry - circle of Willis

2.     Etiological classifications

a)     Atherosclerotic (abdominal) aneurysm

i.              Most common cause of aneurysm

ii.         Clinical complications

1)     Occlusion of nearby arteries

2)     Embolization

3)     Tumor stimulation

4)     Erosion of adjacent structures

5)     Rupture

b)     Syphilitic Aortitis and aneurysm

i.              Tertiary stage of syphilis

ii.         Always thoracic

iii.    Causes narrowing of vasa vasorum aorta

iv.         Clinical complications

1)     Occlusion of airways

2)     Difficulty in swallowing

3)     Persistent brassy cough (rec. lar. N.)

4)     Pain from bone erosion

5)     Cardiac disease - valvular insufficiency

c)     Aortic Dissection (dissecting hematoma)

i.              Common in males age 40-60 with HTN

ii.         Common in Marfan’s syndrome

iii.    Clinical complications

1)     Double barreled aorta

2)     Cystic medial necrosis

3)     Atherosclerosis

4)     Rupture

5)     Hemorrhage

 

 

 

 

 

 

 

 

 

 

 

III.    Venous disorders

A.     Varicose veins

1.     Result from increased intraluminal pressure and loss of support of vessel wall

2.     Clinical significance

a)     Pain

b)     Incompetent valves ® venous stasis ® increasing pressure ® edema ® impaired circulation ® vulnerability to injury

i.              Trophic changes

ii.         Stasis dermatitis

iii.    Cellulitis

iv.         Ulceration

v.              Thrombosis

vi.         Embolization

vii.    Bleeding

3.     Most common involvement

a)     Lower legs; superficial and deep (DVT)

b)     Hemorrhoids

c)     Esophageal varix

B.     Phlebothrombosis and thrombophlebitis - thrombi that arise in DVT’s.  Note: Trousseau's sign - migratory thrombophlebitis; in patients with cancer, venous thromboses that appear spontaneously in one site, only to disappear with subsequent thromboses in other veins

IV.         Lymphatic disorders

A.      Lymphangitis - infections that spread into the lymphatics

1.     GROUP A b-hemolytic streptococci

2.     Red streaks and tenderness

B.     Lymphedema

1.     1°

a)     Isolated or congenital (familial)

b)     Milroy’s disease - incomplete lymphatics; mostly lower extremity

c)     Lymphedema praecox

i.              Affects mostly females age 10-25

ii.         Starts distal and moves proximal

2.     2° - develop in association with inflammation or cancer

a)     Postinflammatory scarring of lymphatic channels

b)     Spread of malignant neoplasms

c)     Radical surgical procedures

d)     Postradiation fibrosis

e)     Filariasis

C.     Clinical notes

1.     Edema occurs distal to lymph obstruction

2.        Edema can lead to interstitial swelling and fibrosis - peau d'orange

 

V.              Vascular tumors

A.     Hemangiomas

B.     Glomangioma (glomus tumor)

C.     Hemangioendothelioma and angiosarcoma

D.     Kaposi's sarcoma (KS) - three types

1.     Classic KS

a)     Affects elderly men (predominantly Jewish)

b)     Relatively indolent

c)       Red-blue inflamed-looking lesions distal lower extremities

d)     Become more numerous and centripetal and nodular

e)     Three stages

i.              Patch - pink/red/purple macule(s)

ii.         Plaque - raised, larger, violet

iii.    Nodule - mitotic presence

2.     African or endemic KS

a)     Same distribution as Burkitt’s lymphoma

b)     Primarily young black males

3.     Epidemic KS

a)     Seen in aids

b)     90-95% in homosexual men

c)     Incidence is declining

d)     Locally produced growth factors causing unchecked growth of cells

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

THE LUNGS

 

I.              Atelectasis (collapse)

A.     Resorption a  - obstruction prevents air from reaching distal airways

B.     Compression a  (a.k.a. passive or relaxation a~) -associates with accumulations within the plural cavity that mechanically collapse the lung

C.     Microatelectasis (a.k.a. nonobstructive a~) - loss of lung expansion due to a complex set of events (i.e. loss of surfactant)

D.     Contraction a (a.k.a. cicatrization) - fibrotic changes in lung or pleura hamper expansion and increase elastic recoil

II.         Obstructive and restrictive lung diseases - general terms

A.     FVC - forced vital capacity

B.     FEV1 - forced expiratory volume at 1 second (rate)

C.     FEV1/FVC - ratio used to compare obstructive with restrictive

III.    Obstructive lung diseases - FVC is normal; FEV1 decreased; FEV1/FVC resultantly decreased

A.     Asthma - episodic, reversible bronchospasm resulting from an exaggerated bronchoconstrictor response to various stimuli

1.     Triad of asthma - DCW (dyspnea, coughing, wheezing)

2.       Most striking macroscopic finding is occlusion of bronchi and bronchioles by thick, tenacious mucous plugs that contain Curschmann's spirals - whorls off shed epithelium.  Numerous eosinophils and Charcot-Leyden crystals (collections of crystalloids made up of eosinophil proteins) are also present

3.      Status asthmaticus - severe paroxysm that does not respond to therapy and persists for days and even weeks

4.     Extrinsic

a)     Type I hypersensitivity reaction from extrinsic antigen

b)     Three types

i.              Atopic asthma

1)     Most common extrinsic

2)     Key players - IgE, mast cells, and eosinophils

ii.         Occupational asthma

iii.    Allergic bronchopulmonary aspergillosis

5.     Intrinsic

a)     Nonimmune triggering mechanisms

b)      Caused by aspirin, infections, cold, stress, exercise

B.     COPD

1.     Emphysema

a)       Permanent enlargement of airspaces distal to the terminal bronchioles accompanied by destruction of their walls

b)     Three types

i.              Panacinar (panlobular) - apical lung

ii.         Centriacinar (centrilobular) - lower lung

iii.      Distal acinar (paraseptal) - adjacent to pleura

 

c)     There is a clear association between heavy cigarette smoking and emphysema

i.                Smokers accumulate neutrophils and macro's in alveoli

ii.         Neutrophil release elastase b/c of smoking

iii.      Macro’s elastase activity enhances b/c of smoking

iv.         Smoke oxidants inhibit antielastase activity

d)      Occurs by excess protease or elastase activity unopposed by appropriate antiprotease/antielastase regulation.  This results in elastic tissue damage and emphysema

e)      Pink puffers - b/c of prominent dyspnea and adequate oxygenation of hemoglobin - often barrel-chested

f)      Blue bloaters - emphysema with chronic bronchitis, with history of recurrent infections with purulent sputum, retain co2 and become hypoxic and cyanotic - often obese

2.     Chronic bronchitis

a)    Persistent productive cough for at least 3 consecutive months in at least 2 consecutive years

b)    Forms: simple, chronic mucopurulent, chronic, asthmatic, chronic obstructive

C.     Broncheictasis

1.     Permanent dilation of bronchi and bronchioles due to destruction of the muscle and elastic supporting tissue, resulting from or associated with chronic necrotizing infections

2.      Causes:

a)     Bronchial obstruction

b)      Congenital or hereditary conditions

i.              Cystic fibrosis - most common cause in U.S.

ii.           Immunodeficiency

iii.      Kartagener's syndrome - abnormalities of cilia

c)     Necrotizing, or suppurative, pneumonia

IV.         Restrictive lung diseases - FVC is reduced; FEV1 normal or decreased; FEV1/FVC resultantly near normal

A.    Extra-pulmonary disorders - affect the ability of the chest wall to act as bellows (obesity, kyphoscoliosis)

B.     Characterized by reduced compliance

C.     Acute restrictive lung diseases – ARDS

1.     Acute onset of respiratory distress

2.      Decreased arterial oxygen pressure

3.      Decreased lung compliance

4.      Development of diffuse pulmonary infiltrates on x-ray

5.      Diffuse alveolar damage is the morphologic counterpart

6.      Most characteristic finding - hyaline membranes, particularly lining the distended alveolar ducts

7.      leads to honeycomb lung

 

 

 

D.     Chronic restrictive lung diseases

1.      Idiopathic pulmonary fibrosis (IPF)

2.      Sarcoidosis

a)      Multisystem disease of unknown cause characterized by noncaseating granulomas in many tissues and organs

b)      Diagnosis is one of exclusion

i.               Patients manifest cutaneous anergy to common test antigens

ii.           T lymphocytes often decreased

iii.        Bronchoalveolar lavage shows increased T lymphocytes

iv.           Normal number B cells, but excess Ig's

c)      Lymph node (hilar and paratracheal) involvement; X-ray shows noncaseating granulomas (key suggestive pathology)

d)      Lung involvement with pulmonary infiltrates and hilar adenopathy x-ray visible

e)      Skin lesions

f)      Eye, lacrimal and salivary glands with iritis or iridocyclitis, inflammation w/o tears, and Mikulicz's syndrome - combined uveoparotid involvement

g)      Spleen and liver granulomas

h)      Other

3.      Hypersensitivity pneumonitis

a)      Immunologically mediated inflammatory lung disease primarily affecting the alveoli - allergic alveolitis

b)      Acute reaction with fever, cough, dyspnea and constitutional complaints

c)      Chronic disease with insidious onset of cough, dyspnea, malaise, and weight loss

4.      Diffuse pulmonary hemorrhage syndromes

a)      Goodpasture7s syndrome - Crescentic glomerulonephritis and hemorrhagic interstitial pneumonitis

b)      Idiopathic pulmonary hemosiderosis

c)      Vasculitis-associated hemorrhage

V.               Vascular lung diseases

A.      Pulmonary thromboembolism, hemorrhage, and infarction

1.      More than 95% of all pulmonary emboli arise from DVT's, popliteal and above

2.      The majority are non-symptomatic, or clinically silent

3.      Less than 5% of cases result in sudden death

4.       Patients that experience one P E have a 30% chance of a second

5.      Nutrient sources

a)      Pulmonary arteries

b)      Bronchial arteries

c)      Directly from alveolar air

B.     Pulmonary hypertension and vascular sclerosis

 

 

 

 

 

 

VI.         Pulmonary infections

A.     Acute bacterial pneumonias

1.       Lobar pneumonia - contiguous airspaces of part or all of a lobe are homogeneously filled with an exudate visible on radiographs as a lobar or segmental consolidation (solidification)

a)       S. pneumoniae (serotype 3) produce 90% of lobar pneumonias; also Klebsiella, mycoplasmas, Legionella pneumophila

b)      Four stages: congestion, red (liver-like) then gray (dry, gray, and firm) hepatization, and resolution

2.      Bronchopneumonia - implies a patchy distribution of inflammation that generally involves more than one lobe

a)     Distribute in yellow patches throughout the lung

b)      Haemophilus influenzae, S. aureus, P. aeruginosa, Moraxella catarrhalis

3.     Complications: abscess, empyema, develop to fibrous tissue, meningitis, arthritis or infective endocarditis Note: aspiration bronchopneumonia

B.      Primary atypical pneumonias; mycoplasmas apparently the cause

C.      Actinomycosis and Nocardiosis

D.      TB

1.     TB infection

a)     Seeding of some focus with organisms that may or may not cause pathology

b)      Detectable by Mantoux test

c)      A positive TB test signifies cell-mediated hypersensitivity to TB antigen

2.     Primary TB

a)      Develops in a previously unexposed, unsensitized person

b)      Ghon focus - 1-1.5cm area of gray-white inflammat6ry consolidation in lung

c)      Ghon complex - combination of parenchymal lesion and nodal involvement

d)      Sometimes cavitates and spreads thru airways or lymphatics to multiple lung sites

e)      Miliary TB - spread of TB through blood

3.     Secondary TB (reactivation TB)

a)     Pattern of TB that arises in a previously sensitized host

b)      Classical localized to the apex of one or both upper lobes; AIDS - cavitation is distinctly uncommon and mediastinal lymphadenopathy usually occurs

c)      Miliary pulmonary disease - drain thru lymphatics into lymphatic ducts to right heart and into pulmonary arteries and lungs

d)      Pott's disease - TB of the vertebrae

 

 

 

 

E.     Fungal infections

1.     Histoplasmosis

a)     Ohio, Mississippi, Appalachian

b)      Mimics TB clinically and histologically

c)      Infect and multiply in phagocytes

2.     Coccidioidomycosis

a)      C. immitis - Valley fever; endemic to San Joaquin Valley

b)      Like histoplasmosis and TB:

i.              Asymptomatic pulmonary infection

ii.           Progressive pulmonary disease

iii.      Miliary disease

3.     Candidiasis

4.      Other Fungal infections

F.     Lung abscess

G.      CMV

H.      Pneumoncystis pneumonia

VII.    Lung tumors

A.     "Coin" lesion - hamartoma that shows up on x-ray

B.      Bronchogenic carcinoma

1.     Four types in two categories

a)     NSCLC (non-small cell lung CA)

i.              Squamous cell carcinoma - often associates with hypercalcemia and correlates with smoking

ii.            Adenocarcinoma - common among nonsmoking women under age 40, often associate with hematologic syndromes

iii.      Large cell undifferentiated carcinoma

b)     SCLC (only small cell carcinoma)

i.              Strong connection with smoking

ii.           Oat cell carcinoma - small, dark, round-to-oval, lymphocyte-like cells that have scant cytoplasm and hyperchromatic nuclei, among which mitoses are numerous

iii.      Rarely resectable

iv.           Best genetic alteration description for this type of cancer:

1)     Amplification of the myc family of oncogene

2)      Mutational activation of tumor suppressor genes p53 and Rb

3)      Mutations of K-ras associate with adenocarcinomas, not SCLC's

C.     Bronchial carcinoid - not a carcinoma, just a slow-growing lesion, usually in the hilar region

 

 

 

 

 

 

 

VIII.                       Pleural lesions

A.     Malignant mesothelioma - amphibole (long, straight) asbestos exposure

B.     Pleural effusion and pleuritis

1.     Hydrothorax - transudate effusion

2.     Result from microbial invasion, cancer, bronchogenic infarct, and viral pleuritis

C.     Pneumothorax, hemothorax, and chylothorax

IX.         Lesions of the upper respiratory tract

A.     Acute infections

B.     Nasopharyngeal carcinoma

C.     Laryngeal tumors

1.     Nonmalignant lesions – polyps

2.     Carcinoma of the larynx

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

THE KIDNEYS

 

I. Clinical manifestations of renal diseases

A.       Azotemia - elevated BUN and creatinine

B.       Acute nephritic syndrome - glomerular syndrome dominated by the acute onset of usually grossly visible hematuria, mild to moderate proteinuria, and HTN

C.       Nephrotic syndrome - heavy proteinuria, hypoalbuminemia, severe edema, hyperlipidemia, and lipiduria

D.       Asymptomatic hematuria or proteinuria - subtle or mild glomerular abnormalities

E.       Acute renal failure - dominated by oliguria with recent onset of azotemia

F.       Chronic renal failure     - prolonged clinicals of uremia

G.       Urinary tract infection

H.       Nephrolithiasis

II. Glomerular diseases

A.     1° glomerulonephritis - kidney is the only or predominant organ involved

1.       Acute diffuse proliferative glomerulonephritis

2.       Rapidly progressive (crescentic) GN

3.       Membranous GN

4.       Lipoid nephrosis (minimal change disease)

5.       Focal segmental glomerulosclerosis

6.       Membranoproliferative GN

7.       IgA nephropathy

8.       Chronic GN

B.     2° glomerulonephritis diseases that effect the kidney secondarily

1.       SLE

2.       Diabetes mellitus

3.       Amyloidosis

4.       Goodpasture's syndrome

5.       Polyarteritis Nodosa

6.       Wegener’s granulomatosis

7.       Henoch-Schönlein purpura

8.       Bacterial endocarditis

C.     Pathogenesis

1.       Circulating immune complex nephritis

a)     Ag + Ab complex in plasma deposits in a granular manner between the endothelium and basement membrane

b)     Granular immunoflourescence of GBM

2.       Immune complex nephritis in situ

a)       Anti-GBM nephritis

i.                Ab in plasma enters the basement membrane and binds with Ag within basement membrane

ii.            Smooth immunoflourescence of GBM

b)      Heymann's nephritis

i.               Ab in plasma passes through basement membrane and binds with Ag in the pedicels

ii.           Granular immunoflourescence of GBM

3.      Cell-mediated immune glomerulonephritis

4.      Mediators of immune injury (reduced filtration rate)

a)      monocytes and macrophages

b)      Platelets

c)      Resident glomerular cells

d)      Fibrin-related products

5.      Other mechanisms of glomerular injury

a)      Epithelial cell injury

b)      Renal ablation glomerulopathy

D.     Glomerular syndromes and disorders

1.      Nephrotic syndrome

a)      Minimal change disease (lipoid nephrosis) glomeruli that have a normal appearance under the light microscope but disclose diffuse loss of visceral epithelial foot processes when viewed with the electron microscope

b)      Membranous glomerulonephritis
Presence of subepithelial immunoglobulin-containing deposit along the GBM

c)      Focal segmental glomerulosclerosis
Sclerosis affecting some but not all glomeruli and involving only segment of each glomerulus

d)      Membranoproliferative glomerulonephritis

i.               Altered basement membrane and mesangium and by proliferation of glomerular cells

ii.           Light microscopy show a double-contour or "tramtrack" appearance resulting from a splitting of the basement membrane by mesangial cells

2.      Nephritic syndrome - typically hematuria, oliguria, and HTN

a)    Acute proliferative glomerulonephritis

i.               a.k.a. Poststreptococcal or Postinfectious glomerulonephritis, perhaps even Diffuse Proliferative Glomerulonephritis

ii.           Smokey brown urine

b)    Rapidly progressive (crescentic) - Presence of crescents in most of the glomeruli b/c or proliferation of parietal epithelial cells of Bowman's capsule and monocytes/macrophages.
Common denominator - sever glomerular Injury

i.                Type I RPGN (Anti-GBM disease)

1)       Idiopathic

2)       Goodpasture's syndrome

 

 

 

ii.            Type II RPGN (Immune complex-mediated disease)

1)       Idiopathic

2)       SLE

3)       Post infectious

4)       Henoch-Schönlein purpura

iii.      Type III RPGN (Pauci-immune or lack of Anti-GBM)

1)     Idiopathic

2)      Wegener's granulomatosis

3)      Polyarteritis

c)      IgA Nephropathy (Berger's disease)

i.                Most common causes of recurrent microscopic or gross hematuria and most common glomerular disease worldwide

ii.            Hallmark is deposition of IgA in the mesangium

d)      Hereditary nephritis - Alport's syndrome

3.      Chronic glomerulonephritis - by the time of presentation, glomerular changes so advance that it is difficult to discern the nature of the original lesion

III. Diseases affecting tubules and interstitium

A.      Tubulointerstitial nephritis

1.      Acute pyelonephritis

a)      Principle causes: Enteric G(-) rods (E. coil, Proteus, Klebsiella, Enterobacter, Pseudomonas)

b)      Two routes: hematogenous and ascending from lower UTI

2.      Chronic pyelonephritis and reflux nephropathy; common causes:

a)       Chronic obstructive pyelonephritis, recurrent infection superimposed on diffuse or localized obstructive lesions leading to recurrent bouts of renal inflammation and scarring

b)      Reflux nephropathy, superimposition on a congenital vesicouretral reflux and intrarenal reflux

3.      Drug-induced interstitial nephritis

a)      Acute

i.               Adverse reaction to a constantly increasing number of drugs

ii.           Synthetic penicillins, synthetic antibiotics, diuretics, NSAIDS, misc.

b)      Analgesic nephropathy

i.               Often associates with renal papillary necrosis

ii.           Serious complication - transitional cell carcinoma of renal pelvis

B.      Acute tubular necrosis

1.      Destruction of tubular epithelial cells and by acute suppression of renal function (oliguria)

2.      Most common cause of Acute Renal Failure (ARF)

3.      Ischemic ATN; mismatched blood, myoglobinuria

4.       Nephrotoxic ATN; poisons (heavy metals), organic solvents, drugs

IV. Diseases involving blood vessels

A.     Benign nephrosclerosis (hyaline arteriolosclerosis)

B.     Malignant HTN and malignant nephrosclerosis (hyperplastic arteriolosclerosis)

C.     Thrombotic microangiopathies; microangiopathic hemolytic anemia, thrombocytopenia, and renal failure

VI.         Cystic diseases of the kidney

A.     Simple cysts; generally innocuous

B.     Autosomal dominant (adult) polycystic kidney disease (APKD) Multiple expanding cysts of both kidneys that ultimately destroy the intervening parenchyma

C.     Autosomal recessive (childhood) polycystic kidney disease Multiple epithelium-lined cysts in the liver as well as proliferation of portal bile ducts

VII.    Urinary outflow obstruction

A.     Renal stones (urolithiasis)

1.     Most common: calcium oxalate mixed with calcium phosphate

2.     Factors important in developing stones

a)     Increased urine concentration of the stone's constituents, to that it exceeds their solubility in urine

b)     Excess calcium absorption in gut w/o hypercalcemia

c)     Hypercalcemia with excess excretion into UTI b/c of:

i.              Hyperparathyroidism

ii.         Vitamin D intoxication

iii.    Sarcoidosis

d)     Excessive excretion of uric acid in urine

3.     Magnesium ammonium phosphate (struvite) stones - alkaline urine, owing to UTI's

4.     May produce unilateral or bilateral

5.     Staghorn calculi - in renal calyceal system

B.     Hydronephrosis

1.     Dilation of the renal pelvis and calyces

2.     Congenital; atresia, valve formations, compression

3.     Acquired; foreign bodies, tumors, inflammation, neurogenic, pregnancy

VIII.                       Tumors

A.     Triad of symptoms

1.     Painless hematuria

2.     Long-standing fever

3.     Dull flank pain

B.     Renal cell carcinomas

1.     Most common tumor in adults

2.     Greater frequency in cigarette smokers, and familial forms

3.     von Hippel-Lindau syndrome (VHL), hemangioblastomas of the CNS and retina; often develop bilateral, often multiple renal cell carcinomas

C.     Wilms' tumor; childhood kidney tumor

D.     Tumors of the urinary bladder and collecting system

1.     Papillomas

2.         Carcinomas

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