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General Pathology

HYPERTENSIVE VASCULAR DISEASE 

Malignant hypertension 
A small percentage of HTN patients (5%) present with a rapidly rising blood pressure that, if untreated, leads to death within 1 to 2 years. 

systolic pressures -> 200 mm Hg or diastolic pressures -> 120 mm Hg 
Associated with renal failure and retinal hemorrhages
Most commonly is superimposed on preexisting benign hypertension

Hypertension (HTN) has the following complications

- stroke (CVD) 
- multi-infarct dementia
- atherosclerotic coronary heart disease 
- cardiac hypertrophy and heart failure (hypertensive heart disease) 
- aortic dissection 
- renal failure

Essential HTN Accounts for 90% to 95% of all cases


SecondaryHTN 

Renal - > Acute glomerulonephritis Chronic renal disease 
Endocrine - >  Cushing syndrome, Hypothyroidism (myxedema) Hyperthyroidism (thyrotoxicosis) Pregnancy-induced (pre-eclampsia)
Cardiovascular  - > Coarctation of aorta 

Neurologic

Psychogenic,  Increased intracranial pressure 

PATHOGENESIS
most cases (95%) are idiopathic (essential hypertension)
Most of the remaining cases (secondary hypertension) are due to primary renal disease, renal artery narrowing 
Gene defects in enzymes involved in aldosterone metabolism 
 Mutations in proteins that affect sodium resorption as in Liddle syndrome
 
 Genetic factors - > familial clustering of hypertension 
 
 Environmental factors such as stress, obesity, smoking, physical inactivity, and high levels of salt consumption, modify the impact of genetic determinants

Morphology
HTN is associated with arteriolosclerosis (small arterial disease) 

Two forms of small blood vessel disease are hypertension-related: 
1- hyaline arteriolosclerosis 
2- hyperplastic arteriolosclerosis 

Hyaline arteriolosclerosis
Associated with benign hypertension. 
-marked by homogeneous, pink hyaline thickening of the arteriolar walls, and luminal narrowing. 

Hyperplastic arteriolosclerosis
It is more typical of severe hypertension. 
- "onionskin," concentric, laminated thickening of arteriolar walls and luminal narrowing. 
- The laminations consist of smooth muscle cells and thickened, reduplicated basement membrane. 

DISORDERS OF BLOOD VESSEL HYPERREACTIVITY
Several disorders are characterized by inappropriate or exaggerated vasoconstriction of blood vessels: 
1- Raynaud Phenomenon 
2- Myocardial Vessel Vasospasm 

Raynaud Phenomenon
- results from exaggerated vasoconstriction of arteries and arterioles in the extremities (the fingers and toes, but also sometimes the nose, earlobes, or lips). 
-restricted blood flow induces paroxysmal pallor or cyanosis
- involved digits characteristically show "red-white-andblue" color changes from most proximal to most distal 

Myocardial Vessel Vasospasm 

Causes: 1- vasoactive mediators - > prolonged vascular contraction; 
- endogenous (e.g., epinephrine released by pheochromocytomas) or exogenous (cocaine or phenylephrine). 
2- Elevated thyroid hormone -> increase sensitivity of vessels to catecholamines 
3- autoantibodies and T cells in scleroderma vascular instability and vasospasm. 
4- extreme psychological stress (release of catecholamines)

Cardiac raynaud

When vasospasm of cardiac arterial or arteriolar bed is of sufficient duration (20 to 30 min ) myocardial infarction occurs

acute microscopic area of necrosis characterized by mycotic hypercontraction (contraction band necrosis)

subacute and chronic cases - > microscopic foci of granulation tissue or scar

Hereditary spherocytosis.

Functionally normal cells which are destroyed .in spleen because of the structural abnormality. It is transmitted as an autosomal dominant trait 

Congenital hemolytic anemia due to genetically determined abnormal spectrin and ankyrin molecules, leading to defects in red blood cell membrane, causing spherical shape and lack of plasticity
Red blood cells become trapped within spleen and have less than usual 120 day lifespan
Splenic function is normal
Osmotic fragility: increased; basis for diagnostic testing 

Description

Firm, deep red tissue, thin capsule, no grossly identifiable malpighian follicles, 100-1000g
Peripheral blood images
Marked congestion in cords
Sinuses appear empty but actually contain ghost red blood cells
May have prominent endothelial lined sinuses, hemosiderin deposition, erythrophagocytosis

Str. agalactiae

β-hemolytic, with its capsule being the major virulence factor.  Capsule inhibits phagocytosis and complement activation.  The CAMP factor (a hemolysin) is another virulence factor.

Group B strep are normally found in GI tracts and vaginas. 

Major disease is neonatal sepsis/meningitis after passage through infected birth canal.  May lead to meningitis, and CNS damage is high.  Mothers colonized with Group B strep should be treated pre-delivery.

Enterococci

Most common are E. fecalis and E. fecium.  Cause inflammation at site of colonization.

Serious resistance to antibiotics.  E. fecium is now a vancomycin resistant enterococcus (VRE)

Post viral (post hepatitic) cirrhosis (15-20%) 

Cause:- Viral hepatitis (mostly HBV or HCV) 
Acute hepatitis  → chronic hepatitis → cirrhosis.  

Pathology
Liver is shrunken.  Fatty change is absent (except with HCV). Cirrhosis is mixed.

M/E  :-
Hepatocytes-show degeneration, necrosis  as other types of cirrhosis. 
Fibrous septa   -They are thick and immature (more cellular and vascular).
- Irregular margins (piece meal necrosis).
- Heavy lymphocytic infiltrate.

Prognosis:- - More rapid course than alcoholic cirrhosis.Hepatocellular carcinoma is more liable to occur 
 

Leukaemias
Uncontrolled proliferation of leukocyte precursors (may be with associated red cell and platelet series proliferation).

Factors which may playa causal role are.
- Viral
- Radiation.
- Genetic.

Classification

1. Acule leukaemia:

a. Lymphocytic (lymphoblastic).
b. Myelocytic and promyelocytic (myeloblastic).
c. Monocytic.
d. Myelomonocytic.
e. Undifferentiated (Stem cell).

2. Chronic leukaemia:

a. Lymphocytic
b. Myelocytic

3. Miscellaneous:
a. Erythroleukaemia (De Guglielmo's disease).
b. Eosinophilic leukaemia.
c. Megakaryocytic leukaemia.

Chickenpox (varicella)
 - primarily a childhood disease (70%)
 - incubation period 14-16 days; highly contagious; infectious 2 days before the vesicles until the last one dries.
 - present with generalized, intensely pruritic skin lesions starting as macules vesicles pustules (MVP-most valuable player) usually traveling centrifugally to the face and out to the extremities; unlike smallpox vesicles, chickenpox vesicles appear in varying stages of development as successive crops of lesions appear; intranuclear inclusions similar to HSV.
 - pneumonia develops in 1/3 of adults; MCC death in chickenpox.
 - association with Reye's syndrome if child takes aspirin. 

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